脂蛋白a与缺血性脑卒中的研究进展
Advanced Research on Lp(a) and Ischemic Stroke
DOI: 10.12677/ACM.2023.1361255, PDF,   
作者: 林 洁:山东大学齐鲁医学院,山东 济南;王爱华*:山东大学齐鲁医学院,山东 济南;山东省千佛山医院神经病学科,山东 济南
关键词: 脂蛋白a缺血性脑卒中综述Lipoprotein (a) Ischemic Stroke Review
摘要: 脑卒中是目前导致人类死亡的第二大原因,也是造成成年人残疾的主要原因,超过半数幸存者遗留不同程度的残疾。积极预防及治疗脑卒中至关重要。血脂水平升高,尤其低密度脂蛋白胆固醇(LDL-C)浓度增加已被公认为脑动脉粥样硬化与缺血性脑卒中的危险因素,但将LDL-C水平控制在指南目标值内仍存在脑卒中残余风险。脂蛋白a [Lp(a)]是一种脂质蛋白复合体,结构与低密度脂蛋白(LDL)类似,可以促进泡沫细胞形成、斑块中脂质的沉积以及血栓形成和炎症反应参与动脉粥样硬化的形成,与缺血性脑卒中的风险及预后关系密切。本文就Lp(a)的结构与作用机制、影响因素、检测方法、与缺血性卒中的关系及治疗方法进行概述。
Abstract: Stroke is currently the second leading cause of human death and the major cause of disability in adults, with more than half of survivors left with varying degrees of disability. Positive prevention and treatment of stroke is essential. Elevated lipid levels, especially increased concentrations of low-density lipoprotein cholesterol (LDL-C), are recognized as risk factor for cerebral atherosclerosis and ischemic stroke, but there is still a remaining risk of stroke when LDL-C levels are limited to the guideline target values. Lipoprotein (a) is a lipid protein complex with a structure similar to that of LDL that promotes foam cell formation, deposition of lipids in plaques, and thrombosis and inflam-matory responses involved in atherosclerosis, and is closely related to the risk and prognosis of is-chemic stroke. This article provides an overview of the structure and mechanism of the effects of Lp(a), factors of its impact, detection methods, relationship with ischemic stroke, and therapeutic approaches.
文章引用:林洁, 王爱华. 脂蛋白a与缺血性脑卒中的研究进展[J]. 临床医学进展, 2023, 13(6): 8966-8972. https://doi.org/10.12677/ACM.2023.1361255

参考文献

[1] Katan, M. and Luft, A. (2018) Global Burden of Stroke. Seminars in Neurology, 38, 208-211. [Google Scholar] [CrossRef] [PubMed]
[2] 贾建平. 神经病学[M]. 第8版. 北京: 人民卫生出版社, 2018: 190-191.
[3] Kamstrup, P.R. (2021) Lipoprotein(a) and Cardiovascular Disease. Clinical Chemistry, 67, 154-166. [Google Scholar] [CrossRef] [PubMed]
[4] 脂蛋白(a)与心血管疾病风险关系及临床管理的专家科学建议[J]. 中国循环杂志, 2021, 36(12): 1158-1167.
[5] Afshar, M. and Thanassoulis, G. (2017) Lipoprotein(a): New In-sights from Modern Genomics. Current Opinion in Lipidology, 28, 170-176. [Google Scholar] [CrossRef
[6] Reyes-Soffer, G. and Westerterp, M. (2021) Beyond Lipo-protein(a) Plasma Measurements: Lipoprotein(a) and Inflammation. Pharmacological Research, 169, Article ID: 105689. [Google Scholar] [CrossRef] [PubMed]
[7] Kronenberg, F., Mora, S., Stroes, E.S.G., et al. (2022) Lipopro-tein(a) in Atherosclerotic Cardiovascular Disease and Aortic Stenosis: A European Atherosclerosis Society Consensus Statement. European Heart Journal, 43, 3925-3946. [Google Scholar] [CrossRef] [PubMed]
[8] Kronenberg, F. (2014) Lipoprotein(a) in Various Conditions: To Keep a Sense of Proportions. Atherosclerosis, 234, 249-251. [Google Scholar] [CrossRef] [PubMed]
[9] Kronenberg, F. (2022) Lipoprotein(a). In: von Eckard-stein, A. and Binder, C.J., Eds., Prevention and Treatment of Atherosclerosis, Handbook of Experimental Pharmacology, Vol. 270, Springer, Cham, 201-232. [Google Scholar] [CrossRef] [PubMed]
[10] Coassin, S., Erhart, G., Weissensteiner, H., et al. (2017) A Novel but Frequent Variant in LPA KIV-2 Is Associated with a Pronounced Lp(a) and Cardiovascular Risk Reduction. European Heart Journal, 38, 1823-1831. [Google Scholar] [CrossRef] [PubMed]
[11] Hopewell, J.C., Haynes, R. and Baigent, C. (2018) The Role of Lip-oprotein (a) in Chronic Kidney Disease. Journal of Lipid Research, 59, 577-585. [Google Scholar] [CrossRef
[12] Kronenberg, F. (2014) Causes and Consequences of Lipoprotein(a) Ab-normalities in Kidney Disease. Clinical and Experimental Nephrology, 18, 234-237. [Google Scholar] [CrossRef] [PubMed]
[13] Simony, S.B., Mortensen, M.B., Langsted, A., Afzal, S., Kam-strup, P.R. and Nordestgaard, B.G. (2022) Sex Differences of Lipoprotein(a) Levels and Associated Risk of Morbidity and Mortality by Age: The Copenhagen General Population Study. Atherosclerosis, 355, 76-82. [Google Scholar] [CrossRef] [PubMed]
[14] Paré, G., Çak, A., McQueen, M., et al. (2019) Lipo-protein(a) Levels and the Risk of Myocardial Infarction Among 7 Ethnic Groups. Circulation, 139, 1472-1482. [Google Scholar] [CrossRef
[15] Enkhmaa, B. and Berglund, L. (2022) Non-Genetic Influences on Lipoprotein(a) Concentrations. Atherosclerosis, 349, 53-62. [Google Scholar] [CrossRef] [PubMed]
[16] Milionis, H.J., Elisaf, M.S., Tselepis, A., Bairaktari, E., Karabina, S.A. and Siamopoulos, K.C. (1999) Apolipoprotein(a) Phenotypes and Lipoprotein(a) Concentrations in Pa-tients with Renal Failure. American Journal of Kidney Diseases, 33, 1100-1106. [Google Scholar] [CrossRef
[17] Gregory, W.L., Game, F.L., Farrer, M., Idle, J.R., Laker, M.F. and James, O.F. (1994) Reduced Serum Lipoprotein(a) Levels in Patients with Primary Biliary Cirrhosis. Athero-sclerosis, 105, 43-50. [Google Scholar] [CrossRef
[18] Wilson, D.P., Jacobson, T.A., Jones, P.H., et al. (2022) Use of Lipoprotein(a) in Clinical Practice: A Biomarker Whose Time Has Come. A Scientific Statement from the National Li-pid Association. Journal of Clinical Lipidology, 16, e77-e95. [Google Scholar] [CrossRef] [PubMed]
[19] 冯仁丰. 脂蛋白(a)检测的标准化[J]. 检验医学, 2017, 32(7): 555-560.
[20] Marcovina, S.M. and Albers, J.J. (2016) Lipoprotein (a) Measurements for Clinical Application. Journal of Lipid Research, 57, 526-537. [Google Scholar] [CrossRef
[21] Rigal, M., Ruidavets, J. B., Viguier, A., Petit, R., Perret, B., Ferrieres, J. and Larrue, V. (2007) Lipoprotein (a) and Risk of Ischemic Stroke in Young Adults. Journal of the Neurological Sciences, 252, 39-44. [Google Scholar] [CrossRef] [PubMed]
[22] Zhang, J., Du, R., Peng, K., et al. (2019) Serum Lipoprotein (a) Is Associated with Increased Risk of Stroke in Chinese Adults: A Prospective Study. Atherosclerosis, 289, 8-13. [Google Scholar] [CrossRef] [PubMed]
[23] Langsted, A., Nordestgaard, B.G. and Kamstrup, P.R. (2019) Elevated Lipoprotein(a) and Risk of Ischemic Stroke. Journal of the American College of Cardiology, 74, 54-66. [Google Scholar] [CrossRef] [PubMed]
[24] Kumar, P., Swarnkar, P., Misra, S. and Nath, M. (2021) Lipopro-tein (a) Level as a Risk Factor for Stroke and Its Subtype: A Systematic Review and Meta-Analysis. Scientific Reports, 11, Article No. 15660. [Google Scholar] [CrossRef] [PubMed]
[25] Lange, K.S., Nave, A.H., Liman, T.G., Grittner, U., Endres, M. and Ebinger, M. (2017) Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke. Stroke, 48, 36-42. [Google Scholar] [CrossRef
[26] Arnold, M., Schweizer, J., Nakas, C.T., et al. (2021) Lipoprotein(a) Is Associated with Large Artery Atherosclerosis Stroke Aetiology and Stroke Recurrence among Patients Below the Age of 60 Years: Results from the Biosignal Study. European Heart Journal, 42, 2186-2196. [Google Scholar] [CrossRef] [PubMed]
[27] van Dam-Nolen, D.H.K., van Dijk, A.C., Crombag, G.A.J.C., et al. (2021) Lipoprotein(a) Levels and Atherosclerotic Plaque Characteristics in the Carotid Artery: The Plaque at RISK (PARISK) Study. Atherosclerosis, 329, 22-29. [Google Scholar] [CrossRef] [PubMed]
[28] Kim, B.S., Jung, H.S., Bang, O.Y., Chung, C.S., Lee, K.H. and Kim, G.M. (2010) Elevated Serum Lipoprotein(a) as a Potential Predictor for Combined Intracranial and Extra-cranial Artery Stenosis in Patients with Ischemic Stroke. Atherosclerosis, 212, 682-688. [Google Scholar] [CrossRef] [PubMed]
[29] Tsimikas, S., Gordts, P.L.S.M., Nora, C., Yeang, C. and Witztum, J.L. (2020) Statin Therapy Increases Lipoprotein(a) Levels. European Heart Journal, 41, 2275-2284. [Google Scholar] [CrossRef] [PubMed]
[30] Sahebkar, A., Simental-Mendía L.E., Watts, G.F., et al. (2017) Com-parison of the Effects of Fibrates Versus Statins on Plasma Lipoprotein(a) Concentrations: A Systematic Review and Meta-Analysis of Head-to-Head Randomized Controlled Trials. BMC Medicine, 15, Article No. 22. [Google Scholar] [CrossRef] [PubMed]
[31] Gaeta, G., Lanero, S., Barra, S., Silvestri, N., Cuomo, V., Ma-terazzi, C. and Vitagliano, G. (2011) Sex Hormones and Lipoprotein(a) Concentration. Expert Opinion on Investigational Drugs, 20, 221-238. [Google Scholar] [CrossRef] [PubMed]
[32] Langsted, A. and Nordestgaard, B.G. (2019) Antisense Oli-gonucleotides Targeting Lipoprotein(a). Current Atherosclerosis Reports, 21, Article No. 30. [Google Scholar] [CrossRef] [PubMed]
[33] Cao, Y.X., Liu, H.H., Li, S., et al. (2019) A Meta-Analysis of the Effect of PCSK9-Monoclonal Antibodies on Circulating Lipoprotein (a) Levels. American Journal of Cardiovascular Drugs, 19, 87-97. [Google Scholar] [CrossRef] [PubMed]
[34] Sahebkar, A., Simental-Mendía, L.E., Stefanutti, C., et al. (2016) Supplementation with Coenzyme Q10 Reduces Plasma Lipoprotein(a) Concentrations but Not other Lipid Indices: A Systematic Review and Meta-Analysis. Pharmacological Research, 105, 198-209. [Google Scholar] [CrossRef] [PubMed]
[35] Schettler, V.J.J., Neumann, C.L., Peter, C., Zimmermann, T., Julius, U., Hohenstein, B., et al. (2019) Lipoprotein Apheresis Is an Optimal Therapeutic Option to Reduce Increased Lp(a) Levels. Clinical Research in Cardiology Supplements, 14, 33-38. [Google Scholar] [CrossRef] [PubMed]
[36] Marcovina, S.M. and Shapiro, M.D. (2022) Measurement of Lipoprotein(a): A Once in a Lifetime Opportunity. Journal of the American College of Cardiology, 79, 629-631. [Google Scholar] [CrossRef] [PubMed]